2010 American Society of Hematology Annual Meeting 3rd - 7th December
Interview with Prof Philippe Moreau - Centre Hospitalier Universitaire de Nantes, France
Administration of bortezomib in multiple myeloma patients
PM Philippe Moreau
IV From time to time a patient on IV therapy with Bortezomib might not be on the ideal approach for that particular patient, so you've been looking at subcu. Can you tell us what you did in this study?
PM Well, Bortezomib is approved in the relapse setting and the labelling of the approval is an IV infusion of the drug. But we know that with IV infusion the drug is very effective but there is some concerns regarding the toxicity, especially the peripheral neuropathy induced by Velcade. So we did a phase III international randomised study comparing subcu with IV. We thought that subcu could be more convenient to the patient – we don't need any IV lines or central lines access; we thought that maybe we wanted to know if the efficacy was similar. So that was a primary endpoint of the study, efficacy. And then we wanted to look at the pharmakinetics, pharmacodynamics, but also at the safety of the subcu infusion.
IV And give me some idea of the scope of the study. How many patients did you have and how many countries?
PM So we have enrolled more than 220 patients in 53 countries and while the primary endpoint was response after four cycles and the response rate is strictly identical comparing IV with subcu - at four cycles but also at the eight cycles, so there is no difference regarding efficacy of both routes of administration. So that’s the first point.
IV So that’s firmly established in the study, yes.
PM Clearly established.
IV And the side-effects and the pharmacodynamics of it?
PM Yes, so pharmacodynamics was also a comparable between the two arms of the study. It means that the protease inhibition was strictly identical as comparing IV versus subcu. But the major finding of the study was that the toxicity was reduced with the subcu infusion. So we do have less neuropathy, grades 3 and 4, but also grades 2, 3 and 4, so we were able to reduce dramatically the incidence of peripheral neuropathy. So we do have a new route of administration of Velcade.
IV And it sounds of course in patients who have relapsed that you may have problems with things like venous access.
PM Yes, well, that’s not a major issue; that’s more convenient, of course. Maybe that will be the basis for future developments of, let’s say, home administration, because right now for Velcade use patients have to go back to the hospital. If there is a possibility to deliver Velcade subcu at home, I think that will be a very important point.
IV You've got a very clear result there. What then, if it’s not obvious, what are the clinical implications?
PM The main clinical implication is that we can maybe use Velcade during a longer period of time because we will have less toxicity and especially peripheral neuropathy. We do... even in patients who are responding to IV Velcade, sometimes we had to stop the drug because it was toxic and inducing peripheral neuropathy. So, in my opinion, that's a really very important finding.
IV How much difference is this going to make in the setting of relapsed disease?
PM Well, this study was performed by physicians. I don't know what will be the decision of the pharmaceutical companies. You know that Velcade is owned in the US by Millennium, in Europe by Johnson, and the two companies have to go now to the agency, FDA and EMEA, to ask for modification of the approval. Right now we have to stick to the approval of the drug, to the labelling of the approval of the drug, so if the company will ask according to the result of this study for the next standard approval of the drug with subcu infusion, then we will be able to use it routinely for subcu.
IV Okay, so it sounds to me as if you're in favour of that though.
PM Of course, yes.
IV Yes, yes. And of course Bortezomib is promising also for first line therapy. Could it be used subcu first line?
PM Yes, there is no reason. If we can use in the relapse setting, we can also use Velcade subcu upfront and you know that, for example, in Europe, Velcade is approved upfront in the combination with MP; that’s the MPV combination which is also one of the standards of care in patients older than 65 years or not eligible for high-dose treatment. So we do have now a new option, let’s say, for the use of Velcade.
IV Now, looking at the whole picture of multiple myeloma, do you see survival being extended, quality of life being improved? Is that actually still possible?
PM I don't think that it will modify the survival of the patients. I think that maybe you can modify the quality of life if patients are now experiencing less peripheral neuropathy, so less toxicity, maybe more convenient – we don't need an IV – and maybe home administration. So maybe that could be... well, that can change somehow with the use of Velcade.
IV Now we’re talking about something which isn't yet licensed, the subcu administration, but what do you think doctors should be thinking about these things, just to sum up?
PM Well, I was invited last week for a medical meeting in the US and I was allowed to present this data on behalf of Millennium and Johnson for a very limited number of physicians, all experts in the field in the US. And they were all so excited by this subcu data that they wanted to use subcu immediately in their hospitals. So I think that the US, maybe the change will be earlier compared with Europe. In Europe we will have to wait for the modification of the approval of the drug.
IV Well, Philippe, it’s a real pleasure getting you here at the American Society of Hematology Annual Meeting in Orlando. Thank you for being on ecancer Television.
PM Thank you so much. Bye.